Osteosarcoma is a primary bone malignancy generally affecting the young, with 60% of cases occurring before the age of 25 years and the peak incidence at 15 years. Survival has improved over the past several decades, with nonmetastatic disease having an approximately 70% chance of long-term survival. Unfortunately, patients with metastatic disease at diagnosis or those who have recurrent disease have a dismal prognosis, with approximately 20% surviving long term. In this review article we describe several new therapies in development for osteosarcoma. These include immune-based therapies, strategies to inhibit tumor growth, radiotherapy, and the introduction of new chemotherapies and targets.